A previous study of 26 Japanese, VHL families was extended to 41 additional families. Germline mutations were detected in 55 of 77 Japanese families using SSCP, direct sequencing, and Southern Blot analysis of peripheral blood samples. The N131S (c.392A>G) missense mutation was found in 1 VHL type 2 family with both family members having retinal angiomas and pheochromocytomas (family ID 87). 1/2 individuals had hemangioblastomas of the central nervous system and 1/2 had pancreatic cysts or tumor (unspecified).